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FTO-mediated cytopl...
FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell
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- Relier, Sébastien (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
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- Ripoll, Julie (author)
- LIRMM, Univ. Montpellier, CNRS, Montpellier, France
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- Guillorit, Hélène (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France; Stellate Therapeutics, Paris, France
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- Amalric, Amandine (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
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- Achour, Cyrinne (author)
- Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
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- Boissière, Florence (author)
- ICM, Montpellier, France
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- Vialaret, Jérôme (author)
- IRMB-PPC, Univ. Montpellier, INSERM, CHU Montpellier, CNRS, Montpellier, France; INM, Univ. Montpellier, INSERM, Montpellier, France
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- Attina, Aurore (author)
- IRMB-PPC, Univ. Montpellier, INSERM, CHU Montpellier, CNRS, Montpellier, France; INM, Univ. Montpellier, INSERM, Montpellier, France
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- Debart, Françoise (author)
- IBMM, CNRS, Univ. Montpellier, ENSCM, Montpellier, France
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- Choquet, Armelle (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
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- Macari, Françoise (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
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- Marchand, Virginie (author)
- Université de Lorraine, IMoPA UMR7365 CNRS-UL and UMS2008/US40 IBSLor, UL-CNRS-INSERM, BioPole, Vandoeuvre-les-Nancy, France
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- Motorin, Yuri (author)
- Université de Lorraine, IMoPA UMR7365 CNRS-UL and UMS2008/US40 IBSLor, UL-CNRS-INSERM, BioPole, Vandoeuvre-les-Nancy, France
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- Samalin, Emmanuelle (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France; ICM, Montpellier, France
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- Vasseur, Jean-Jacques (author)
- IBMM, CNRS, Univ. Montpellier, ENSCM, Montpellier, France
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- Pannequin, Julie (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
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- Aguilo, Francesca, PhD (author)
- Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
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- Lopez-Crapez, Evelyne (author)
- ICM, Montpellier, France
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- Hirtz, Christophe (author)
- IRMB-PPC, Univ. Montpellier, INSERM, CHU Montpellier, CNRS, Montpellier, France; INM, Univ. Montpellier, INSERM, Montpellier, France
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- Rivals, Eric (author)
- LIRMM, Univ. Montpellier, CNRS, Montpellier, France
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- Bastide, Amandine (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France
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- David, Alexandre (author)
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France; IRMB-PPC, Univ. Montpellier, INSERM, CHU Montpellier, CNRS, Montpellier, France
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IGF, Univ Montpellier, CNRS, INSERM, Montpellier, France LIRMM, Univ. Montpellier, CNRS, Montpellier, France (creator_code:org_t)
- 2021-03-19
- 2021
- English.
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Abstract
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- Cancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its N6,2’-O-dimethyladenosine (m6Am) demethylase activity. While m6Am is strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Am level in mRNA which results in enhanced in vivo tumorigenicity and chemoresistance. Inhibition of the nuclear m6Am methyltransferase, PCIF1/CAPAM, fully reverses this phenotype, stressing the role of m6Am modification in stem-like properties acquisition. FTO-mediated regulation of m6Am marking constitutes a reversible pathway controlling CSC abilities. Altogether, our findings bring to light the first biological function of the m6Am modification and its potential adverse consequences for colorectal cancer management.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (subject category)
- art (subject category)
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Relier, Sébastie ...
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Ripoll, Julie
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Guillorit, Hélèn ...
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Amalric, Amandin ...
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Achour, Cyrinne
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Boissière, Flore ...
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Vialaret, Jérôme
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Attina, Aurore
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Debart, François ...
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Choquet, Armelle
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Macari, François ...
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Marchand, Virgin ...
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Motorin, Yuri
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Samalin, Emmanue ...
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Vasseur, Jean-Ja ...
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Pannequin, Julie
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Aguilo, Francesc ...
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Lopez-Crapez, Ev ...
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Hirtz, Christoph ...
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Rivals, Eric
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Bastide, Amandin ...
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David, Alexandre
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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Nature Communica ...
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Umeå University